Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19
Authors: Ziad Bakouny, Chris Labaki, Punita Grover, Joy Awosika, Shuchi Gulati, Chih-Yuan Hsu, Saif I. Alimohamed, Babar Bashir, Stephanie Berg, Mehmet A. Bilen, Daniel Bowles, Cecilia Castellano, Aakash Desai, Arielle Elkrief, Omar E. Eton, Leslie A. Fecher, Daniel Flora, Matthew D. Galsky, Margaret E. Gatti-Mays, Alicia Gesenhues, Michael J. Glover, Dharmesh Gopalakrishnan, Shilpa Gupta, Thorvardur R. Halfdanarson, Brandon Hayes-Lattin, Mohamed Hendawi, Emily Hsu, Clara Hwang, Roman Jandarov, Chinmay Jani, Douglas B. Johnson, Monika Joshi, Hina Khan, Shaheer A. Khan, Natalie Knox, Vadim S. Koshkin, Amit A. Kulkarni, Daniel H. Kwon, Sara Matar, Rana R. McKay, Sanjay Mishra, Feras A. Moria, Amanda Nizam, Nora L. Nock, Taylor K. Nonato, Justin Panasci, Lauren Pomerantz, Andrew J. Portuguese, Destie Provenzano, Matthew Puc, Yuan J. Rao, Terence D. Rhodes, Gregory J. Riely, Jacob J. Ripp, Andrea V. Rivera, Erika Ruiz-Garcia, Andrew L. Schmidt, Adam J. Schoenfeld, Gary K. Schwartz, Sumit A. Shah, Justin Shaya, Suki Subbiah, Lisa M. Tachiki, Matthew D. Tucker, Melissa Valdez-Reyes, Lisa B. Weissmann, Michael T. Wotman, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Yuanchu James Yang, Michael A. Thompson, Dimpy P. Shah, Jeremy L. Warner, Yu Shyr, Toni K. Choueiri, Trisha M. Wise-Draper, Ariel Fromowitz, Rikin Gandhi, Benjamin A Gartrell, Sanjay Goel, Balazs Halmos, Della F Makower, Darciann O' Sullivan, Nitin Ohri, Mary Portes, Lauren C Shapiro, Aditi Shastri, R Alejandro Sica, Amit K Verma, Omar Butt, Jian Li Campian, Mark A Fiala, Jeffrey P Henderson, Ryan S Monahan, Keith E Stockerl-Goldstein, Alice Y Zhou, Jacob D Bitran, Sigrun Hallmeyer, Daniel Mundt, Sasirekha Pandravada, Philip V Papaioannou, Mauli Patel, Mitrianna Streckfuss, Eyob Tadesse, Na Tosha N Gatson, Madappa N Kundranda, Philip E Lammers, Jonathan M Loree, Irene S Yu, Poorva Bindal, Barbara Lam, Mary Linton B Peters, Andrew J Piper-Vallillo, Pamela C Egan, Dimitrios Farmakiotis, Panos Arvanitis, Elizabeth J Klein, Adam J Olszewski, Kendra Vieira, Anne H Angevine, Michael H Bar, Salvatore A Del Prete, Maryann Z Fiebach, Anthony P Gulati, Edward Hatton, Kaly Houston, Suzanne J Rose, K M Steve Lo, Jamie Stratton, Paul L Weinstein, Jorge A Garcia, Bertrand Routy, Irma Hoyo-Ulloa, Scott J Dawsey, Christopher A Lemmon, Nathan A Pennell, Nima Sharifi, Corrie A Painter, Carolina Granada, Claire Hoppenot, Ang Li, Danielle S Bitterman, Jean M Connors, George D Demetri, Narjust Florez (Duma), Dory A Freeman, Antonio Giordano, Alicia K Morgans, Anju Nohria, Renee Maria Saliby, Sara M Tolaney, Eliezer M Van Allen, Wenxin Vincent Xu, Rebecca L Zon, Susan Halabi, Tian Zhang, Hannah Dzimitrowicz, John C Leighton, Jerome J Graber, Petros Grivas, Jessica E Hawley, Elizabeth T Loggers, Gary H Lyman, Ryan C Lynch, Elizabeth S Nakasone, Michael T Schweizer, Shaveta Vinayak, Michael J Wagner, Albert Yeh, Yvonne Dansoa, Mina Makary, Jesse J Manikowski, Joseph Vadakara, Kristena Yossef, Jennifer Beckerman, Sharad Goyal, Ian Messing, Lori J Rosenstein, Dawn R Steffes, Susan Alsamarai, Jessica M Clement, Jonathan A Cosin, Ahmad Daher, Mark E Dailey, Rawad Elias, Joshua A Fein, Wylie Hosmer, Asha Jayaraj, Jeff Mather, Alvaro G Menendez, Rajani Nadkarni, Oscar K Serrano, Peter Paul Yu, Nino Balanchivadze, Shirish M Gadgeel, Melissa K Accordino, Divaya Bhutani, Brianne E Bodin, Dawn L Hershman, Cynthia Masson, Mariam Alexander, Sarah Mushtaq, Daniel Y Reuben, Eric H Bernicker, John F Deeken, Kelly J Jeffords, Danielle Shafer, Ana I Cárdenas, Rogelio Cuervo Campos, Daniel De-la-Rosa-Martinez, Ana Ramirez, Diana Vilar-Compte, David M Gill, Mark A Lewis, Clarke A Low, Michelle M Jones, Abdul-Hai Mansoor, Sandeep H Mashru, Mica A Werner, Aaron M Cohen, Shannon McWeeney, Eneida R Nemecek, Staci P Williamson, Solange Peters, Stephanie J Smith, Grant C Lewis, Howard A Zaren, Mojtaba Akhtari, Dan R Castillo, Kimberly Cortez, Eric Lau, Gayathri Nagaraj, Kyu Park, Mark E Reeves, Timothy E O'Connor, Jessica Altman, Michael Gurley, Mary F Mulcahy, Firas H Wehbe, Eric B Durbin, Heather H Nelson, Vidhyalakshmi Ramesh, Zohar Sachs, Grace Wilson, Aditya Bardia, Genevieve Boland, Justin F Gainor, Jeffrey Peppercorn, Kerry L Reynolds, Rachel P Rosovsky, Leyre Zubiri, Tanios S Bekaii-Saab, Michael J Joyner, Irbaz B Riaz, Jonathon  W Senefeld, Surbhi Shah, Susan K Ayre, Mark Bonnen, Daruka Mahadevan, Cindy McKeown, Ruben A Mesa, Amelie G Ramirez, Mary Salazar, Pankil K Shah, Chen-Pin Wang, Nathaniel Bouganim, Jesse Papenburg, Arielle Sabbah, Vicky Tagalakis, Donald C Vinh, Rahul Nanchal, Harpreet Singh, Nadia Bahadur, Ting Bao, Rimma Belenkaya, Puja  H Nambiar, Roisin E O’Cearbhaill, Esperanza B Papadopoulos, John Philip, Mark Robson, Jonathan E Rosenberg, Cy R Wilkins, Rulla Tamimi, Kim Cerrone, Jennifer Dill, Bryan A Faller, Mohammed E Alomar, Sanjay A Chandrasekhar, Emma C Hume, Jessica Y Islam, Archana Ajmera, Sharon S Brouha, Angelo Cabal, Sharon Choi, Albert Hsiao, Jun Yang Jiang, Seth Kligerman, Ji Park, Pedram Razavi, Erin G Reid, Padmanabh S Bhatt, Melissa G Mariano, Carey C Thomson, Mary (Grace) Glace, Jeanna L Knoble, Cameron Rink, Rosemary Zacks, Sibel H Blau, CarrieAnn Brown, Angela Shaw Cantrell, Swathi Namburi, Hyma V Polimera, Marc A Rovito, Natasha Edwin, Katrina Herz, Hagen F Kennecke, Amelia Monfared, Rachel R Sautter, Tara Cronin, Amro Elshoury, Bridget Fleissner, Elizabeth A Griffiths, Francisco Hernandez-Ilizaliturri, Prantesh Jain, Ariffa Kariapper, Ellis Levine, Melissa Moffitt, Tracey L O'Connor, Laurie J Smith, Camille P Wicher, Emese Zsiros, Salma K Jabbour, Christian F Misdary, Mansi R Shah, Gerald Batist, Erin Cook, Cristiano Ferrario, Susie Lau, Wilson  H Miller, Lawrence Rudski, Miriam Santos Dutra, Machelle Wilchesky, Sana Z Mahmood, Christopher McNair, Vasil Mico, Becky Dixon, Goetz Kloecker, Barbara B Logan, Chaitanya Mandapakala, Elwyn C Cabebe, Alokkumar Jha, Ali Raza Khaki, Seema Nagpal, Lidia Schapira, Julie Tsu-Yu Wu, David Whaley, Gilberto de Lima Lopes, Karen de Cardenas, Karen Russell, Brittany Stith, Sharona Taylor, Justin F Klamerus, Sanjay G Revankar, Daniel Addison, James L Chen, Marcy Haynam, Sachin R Jhawar, Vidhya Karivedu, Joshua D Palmer, Clement Pillainayagam, Daniel G Stover, Sarah Wall, Nicole O Williams, Saqib Hussen Abbasi, Sandy Annis, Nicole B Balmaceda, Steven Greenland, Anup Kasi, Crosby D Rock, Matt Luders, Melissa Smits, Matthias Weiss, David D Chism, Susie Owenby, Celina Ang, Deborah B Doroshow, Megan Metzger, Jeffrey Berenberg, Catherine Uyehara, Alyson Fazio, Kathryn E Huber, Latoya N Lashley, Mark H Sueyoshi, Kanishka G Patel, Jonathan Riess, Hala T Borno, Eric J Small, Sylvia Zhang, Tessa M Andermann, Christopher  E Jensen, Samuel M Rubinstein, William A Wood, Syed A Ahmad, Lauren Brownfield, Hannah Heilman, Jordan Kharofa, Tahir Latif, Michelle Marcum, Hira  G Shaikh, Davendra P S Sohal, Maheen Abidi, Christopher L Geiger, Merry-Jennifer Markham, Atlantis  D Russ, Haneen Saker, Jared D Acoba, Horyun Choi, Young Soo Rho, Lawrence E Feldman, Gerald Gantt, Kent F Hoskins, Mahir Khan, Li C Liu, Ryan H Nguyen, Mary M Pasquinelli, Candice Schwartz, Neeta K Venepalli, Praveen Vikas, Yousef Zakharia, Christopher R Friese, Anne Boldt, Cyndi J Gonzalez, Chris Su, Christopher T Su, James J Yoon, Ragneel Bijjula, Blanche H Mavromatis, Mildred E Seletyn, Barbara R Wood, Qamar U Zaman, Virginia Kaklamani, Alicia Beeghly, Alaina J Brown, Lawrence J Charles, Alex Cheng, Marta A Crispens, Sarah Croessmann, Elizabeth J Davis, Tan Ding, Stephany N Duda, Kyle T Enriquez, Benjamin French, Erin A Gillaspie, Daniel J Hausrath, Cassandra Hennessy, Judy T Lewis, Xuanyi (Lexi) Li, Lauren S Prescott, Sonya A Reid, Sara Saif, David A Slosky, Carmen C Solorzano, Tianyi Sun, Karen Vega-Luna, Lucy L Wang, David M Aboulafia, Theresa M Carducci, Karen J Goldsmith, Susan Van Loon, Umit Topaloglu, Joan Moore, Robert L Rice, Wilhelmina D Cabalona, Sandra Cyr, Briana Barrow McCollough, Prakash Peddi, Lane R Rosen, Deepak Ravindranathan, Navid Hafez, Roy S Herbst, Patricia LoRusso, Maryam B Lustberg, Tyler Masters, Catherine Stratton
Journal: JAMA Oncology (2022)

Importance Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration ClinicalTrials.gov Identifier: NCT04354701